- Diabetes Insipidus is a clinical syndrome associated with insufficient secretion or action of Antidiuretic Hormone (ADH) resulting in inappropriate excretion of large amounts of highly dilute urine.
- Diabetes Insipidus can result from reduced posterior pituitary secretion of ADH, referred to as Central DI, or due to reduced renal response to the action of appropriately-secreted ADH, referred to as Nephrogenic DI. These basic etiological categories can be easily clinically distinguished by injecting recombinant ADH which will correct central DI but not nephrogenic DI.
- Central DI
- Central DI may arise in children due to agenesis of the posterior pituitary, inherited mutations of the ADH gene, or progressive degeneration of ADH-secreting neurons.
- In adults, Central DI is typically due to some physical insult to the posterior pituitary. Head trauma, brain surgery, or expansion of a sellar mass such as a pituitary adenoma or craniopharyngioma are all possibilities.
- Nephrogenic DI
- Nephrogenic DI can be inherited as a result of a variety of mutations which may affect the renal ADH-receptor or the aquaporin genes responsible for allowing tubular free water resorption. Alternatively, a variety of drugs, especially lithium, can result in transient nephrogenic DI.
- The syndrome of Diabetes Insipidus is highly predictable given the role of the thirst sensation in ECF Osmoregulation. Briefly, insufficient ADH results in an inability to concentrate urine and thus polyuria of vast amounts of highly dilute urine by the kidneys. This tends to increase the ECF osmolarity thus triggering a powerful sensation of thirst and in turn profound polydypsia of free water. Interestingly, the thirst drive in response to increased ECF osmolarity is so strong that so long as the patient has access to free water the ECF osmolarity will largely stay normal. If access to free water is prevented, progressive hypernatremia will result.